tbuckley/cabot-search huggingface dataset:
The surgical management of diffuse gliomas: Current state of neurosurgical management and future directions
Authors: Jacob S Young, Ramin A Morshed, Shawn L Hervey-Jumper, Mitchel S Berger
Journal: Neuro-Oncology (2023)

Abstract After recent updates to the World Health Organization pathological criteria for diagnosing and grading diffuse gliomas, all major North American and European neuro-oncology societies recommend a maximal safe resection as the initial management of a diffuse glioma. For neurosurgeons to achieve this goal, the surgical plan for both low- and high-grade gliomas should be to perform a supramaximal resection when feasible based on preoperative imaging and the patient’s performance status, utilizing every intraoperative adjunct to minimize postoperative neurological deficits. While the surgical approach and technique can vary, every effort must be taken to identify and preserve functional cortical and subcortical regions. In this summary statement on the current state of the field, we describe the tools and technologies that facilitate the safe removal of diffuse gliomas and highlight intraoperative and postoperative management strategies to minimize complications for these patients. Moreover, we discuss how surgical resections can go beyond cytoreduction by facilitating biological discoveries and improving the local delivery of adjuvant chemo- and radiotherapies.
Trends in Alcohol-Related Deaths by Sex in the US, 1999-2020
Authors: Ibraheem M. Karaye, Nasim Maleki, Nawaal Hassan, Ismaeel Yunusa
Journal: JAMA Network Open (2023)

Importance Alcohol consumption rates have been increasing among women in the US, which may affect mortality rates and sex gaps. Therefore, conducting a comprehensive assessment of sex differences in alcohol-related deaths is essential to inform targeted interventions and policies aimed at reducing the burden of alcohol-related harm among the population. Objective To examine sex differences in the burden and trends of alcohol-related mortality in the US from 1999 to 2020. Design, Setting, and Participants This cross-sectional time series study used Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research data on alcohol-related deaths from 1999 to 2020. Alcohol-related deaths were identified from the underlying cause of death files using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision , codes, including alcohol-related poisoning, liver disease, gastritis, cardiomyopathy, myopathy, polyneuropathy, and pseudo-Cushing syndrome, among others. Main Outcomes and Measures Age-adjusted mortality rates (AAMRs) were analyzed by sex and substratified by race and ethnicity, age, and census region. Rate ratios and 95% CIs calculated by Taylor series were used to assess sex differences in mortality burden. Joinpoint regression was used to assess temporal trends. Results A total of 605 948 alcohol-attributed deaths were identified in the US from 1999 through 2020 (AAMR, 8.3 per 100 000 persons; 95% CI, 8.3-8.3 per 100 000 persons). The mortality burden was higher among male individuals than female individuals, with male individuals being 2.88 (95% CI, 2.86-2.89) times more likely to die compared with female individuals. However, temporal trends showed an increase in alcohol-related deaths for both male and female individuals in recent years, with higher rates of increase among female individuals relative to male individuals. The AAMR increased by 12.5% (95% CI, 6.4%-19.1%) per year among male individuals from 2018 to 2020 but increased by 14.7% (95% CI, 9.1%-20.5%) per year among female individuals during the same period. Trend differences were observed across subtypes of age, race and ethnicity, cause, and region. Conclusions and Relevance This study of alcohol-related mortality in the US suggests there has been a significantly higher rate of increase in deaths among female individuals in recent years. These findings underscore the need for further research to understand the specific factors associated with this trend. The development of targeted interventions and evidence-based treatments for alcohol use among female individuals becomes imperative in effectively addressing the increasing rates of alcohol-related deaths.
A Phase II Study of Durvalumab for Bacillus Calmette-Guerin (BCG) Unresponsive Urothelial Carcinoma <i>In Situ</i> of the Bladder
Authors: Roger Li, Wade J. Sexton, Jasreman Dhillon, Anders Berglund, Shreyas Naidu, Gustavo Borjas, Kyle Rose, Youngchul Kim, Xuefeng Wang, Jose R. Conejo-Garcia, Rohit K. Jain, Michael A. Poch, Philippe E. Spiess, Julio Pow-Sang, Scott M. Gilbert, Jingsong Zhang
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Immune checkpoint blockade holds promise for treating bacillus Calmette-Guerin (BCG)-unresponsive non–muscle-invasive bladder cancer (NMIBC). In this phase II study, we investigated the safety and efficacy of durvalumab, a human IgG1 monoclonal antibody, against BCG-unresponsive carcinoma in situ (CIS). Patients and Methods: Patients with BCG-unresponsive CIS-containing NMIBC received durvalumab IV at 1,500 mg every 4 weeks for up to 12 months. The primary endpoint was complete response (CR) rate at month 6, defined by negative cystoscopy, urine cytology, and absence of high-grade recurrence on bladder mapping biopsy. The null hypothesis specified a CR rate of 18% and alternative hypothesis of 40%. According to the Simon two-stage design, if ≤3/13 patients achieved CR during stage 1, the trial is stopped due to futility. Results: Between March 8, 2017, and January 24, 2020, 17 patients were accrued whereas 4 withdrew from study treatment after bladder biopsy at month 3 was positive for CIS. Two of 17 (12%) achieved a CR at month 6, with duration of response of 10 and 18 months, respectively. A single grade 3 lipase elevation was attributed to durvalumab, and immune-related adverse events were observed in 7/17 (41%) patients. Only 1/17 patients had high programmed death-ligand 1 expression pretreatment. On RNA sequencing, complement activation genes were elevated posttreatment, along with enrichment of tumor-associated macrophage signature. Conclusions: Durvalumab monotherapy conferred minimal efficacy in treating BCG-unresponsive CIS of the bladder, with 6-month CR of 12%. Complement activation is a potential mechanism behind treatment resistance.
Effectiveness of spironolactone for women with acne vulgaris (SAFA) trial: a critically appraised topic
Authors: Ali Shields, John S Barbieri
Journal: British Journal of Dermatology (2023)

Journal Article Corrected proof Effectiveness of spironolactone for women with acne vulgaris (SAFA) trial: a critically appraised topic Get access Ali Shields, Ali Shields Data curation, Investigation, Writing - original draft, Writing - review & editing Department of Dermatology, Brigham and Women’s Hospital, Boston, MA, USADrexel University College of Medicine, Philadelphia, PA, USA Search for other works by this author on: Oxford Academic Google Scholar John S Barbieri John S Barbieri Formal analysis, Investigation, Supervision, Writing - original draft, Writing - review & editing Department of Dermatology, Brigham and Women’s Hospital, Boston, MA, USA Correspondence: John S. Barbieri. Email: jbarbieri@bwh.harvard.edu https://orcid.org/0000-0002-5467-4102 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad270, https://doi.org/10.1093/bjd/ljad270 Published: 28 July 2023 Article history Received: 03 July 2023 Accepted: 24 July 2023 Published: 28 July 2023 Corrected and typeset: 24 August 2023
Screening for liver cancer: The good, the bad, and the ugly
Authors: Ángeles García-Criado, Jordi Bruix
Journal: Hepatology (2023)

1Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS 2Liver Oncology Unit, Department of Radiology, CDI, Hospital Clinic 3Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD) 4University of Barcelona 5Liver Oncology Unit, Liver Unit, ICMDM, Hospital Clinic Correspondence A. García-Criado, Department of Radiology, Hospital Clínic. Email: [email protected]
Accuracy of Electronic Health Record–Documented Aspirin for Primary Prevention in Adult Outpatients
Authors: Naina Chipalkatti, Geoffrey D. Barnes, Adam Davie, Jennifer J. Griggs, Molly Harrod, Christine Medaugh, Jordan K. Schaefer
Journal: JAMA Network Open (2023)

This quality improvement study examines the accuracy of electronic health record (EHR) documentation of aspirin use for primary prevention of atherosclerotic cardiovascular disease in adult outpatients.
Global Association of the COVID-19 Pandemic With Pediatric Clinical Trial Publication
Authors: Sarah Grantham-Hill, Michael Eyre, Athimalaipet V. Ramanan, Neena Modi, Saskia N. de Wildt, Ming Lim
Journal: JAMA Network Open (2023)

This cross-sectional study investigates the association of the COVID-19 pandemic with rates of pediatric clinical trial publication.
Cohesin maintains replication timing to suppress DNA damage on cancer genes
Authors: Jinchun Wu, Yang Liu, Zhengrong Zhangding, Xuhao Liu, Chen Ai, Tingting Gan, Haoxin Liang, Yuefeng Guo, Mohan Chen, Yiyang Liu, Jianhang Yin, Weiwei Zhang, Jiazhi Hu
Journal: Nature Genetics (2023)
<i>ERJ</i>Podcast July 2023: The HISTORIC study
Journal: European Respiratory Journal (2023)

As part of the July issue, the European Respiratory Journal presents the latest in its series of podcasts. Chief Editor James Chalmers interviews Prof. Daiana Stolz about HISTORIC, a randomised, placebo-controlled, double-blind, investigator-initiated trial of airway smooth muscle area to predict steroid responsiveness in COPD patients receiving triple therapy.
PTPN9 dephosphorylates FGFR2pY656/657 through interaction with ACAP1 and ameliorates pemigatinib effect in cholangiocarcinoma
Authors: Liming Zhao, Jialiang Liu, Kangshuai Li, Chao Zhang, Tianli Chen, Zengli Liu, Yongchang Tang, Xiaoqiang Hu, Anda Shi, Lizhuang Shu, Shaohui Huang, Shuo Lian, Minghui Zhang, Hui Li, Jinpeng Sun, Xiao Yu, Zhongyin Zhang, Zongli Zhang, Yunfei Xu
Journal: Hepatology (2023)

Abstract and Aim: Cholangiocarcinoma (CCA) is a highly aggressive and lethal cancer that originates from the biliary epithelium. Systemic treatment options for CCA are currently limited, and the first targeted drug of CCA, pemigatinib, emerged in 2020 for CCA treatment by inhibiting FGFR2 phosphorylation. However, the regulatory mechanism of FGFR2 phosphorylation is not fully elucidated. Approach and Results: Here we screened the FGFR2-interacting proteins and showed that protein tyrosine phosphatase (PTP) N9 interacts with FGFR2 and negatively regulates FGFR2 pY656/657 . Using phosphatase activity assays and modeling the FGFR2-PTPN9 complex structure, we identified FGFR2 pY656/657 as a substrate of PTPN9, and found that sec. 14p domain of PTPN9 interacts with FGFR2 through ACAP1 mediation. Coexpression of PTPN9 and ACAP1 indicates a favorable prognosis for CCA. In addition, we identified key amino acids and motifs involved in the sec. 14p-APCP1-FGFR2 interaction, including the “YRETRRKE” motif of sec. 14p, Y471 of PTPN9, as well as the PH and Arf-GAP domain of ACAP1. Moreover, we discovered that the FGFR2 I654V substitution can decrease PTPN9-FGFR2 interaction and thereby reduce the effectiveness of pemigatinib treatment. Using a series of in vitro and in vivo experiments including patient-derived xenografts (PDX), we showed that PTPN9 synergistically enhances pemigatinib effectiveness and suppresses CCA proliferation, migration, and invasion by inhibiting FGFR2 pY656/657 . Conclusions: Our study identifies PTPN9 as a negative regulator of FGFR2 phosphorylation and a synergistic factor for pemigatinib treatment. The molecular mechanism, oncogenic function, and clinical significance of the PTPN9-ACAP1-FGFR2 complex are revealed, providing more evidence for CCA precision treatment.
Advanced molecular diagnostic tools: A step closer to precision medicine in neuro-oncology
Authors: Elisa Aquilanti, Patrick Y Wen
Journal: Neuro-Oncology (2023)

Journal Article Advanced molecular diagnostic tools: A step closer to precision medicine in neuro-oncology Get access Elisa Aquilanti, Elisa Aquilanti Division of Neuro-Oncology, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USADepartment of Medicine, Harvard Medical School, Boston, MA, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Patrick Y Wen Patrick Y Wen Division of Neuro-Oncology, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USADivision of Neuro-Oncology, Department of Neurology, Brigham and Women’s Hospital, Boston, MA, USADepartment of Neurology, Harvard Medical School, Boston, MA, USA Corresponding Author: Patrick Y. Wen, MD, Division of Neuro Oncology, Dana Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA (patrick_wen@dfci.harvard.edu). https://orcid.org/0000-0002-0774-7700 Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 25, Issue 10, October 2023, Pages 1750–1751, https://doi.org/10.1093/neuonc/noad132 Published: 28 July 2023 Article history Published: 28 July 2023 Corrected and typeset: 19 August 2023
Multidimensional biomarkers for multiple system atrophy: an update and future directions
Authors: Linlin Wan, Sudan Zhu, Zhao Chen, Rong Qiu, Beisha Tang, Hong Jiang
Journal: Translational Neurodegeneration (2023)

Abstract Multiple system atrophy (MSA) is a fatal progressive neurodegenerative disease. Biomarkers are urgently required for MSA to improve the diagnostic and prognostic accuracy in clinic and facilitate the development and monitoring of disease-modifying therapies. In recent years, significant research efforts have been made in exploring multidimensional biomarkers for MSA. However, currently few biomarkers are available in clinic. In this review, we systematically summarize the latest advances in multidimensional biomarkers for MSA, including biomarkers in fluids, tissues and gut microbiota as well as imaging biomarkers. Future directions for exploration of novel biomarkers and promotion of implementation in clinic are also discussed.
Prevalence of Hearing Loss and Hearing Aid Use Among US Medicare Beneficiaries Aged 71 Years and Older
Authors: Nicholas S. Reed, Emmanuel E. Garcia-Morales, Clarice Myers, Alison R. Huang, Joshua R. Ehrlich, Olivia J. Killeen, Julie E. Hoover-Fong, Frank R. Lin, Michelle L. Arnold, Esther S. Oh, Jennifer A. Schrack, Jennifer A. Deal
Journal: JAMA Network Open (2023)

Importance National prevalence estimates are needed to guide and benchmark initiatives to address hearing loss. However, current estimates are not based on samples that include representation of the oldest old US individuals (ie, aged ≥80 years), who are most at-risk of having hearing loss. Objective To estimate the prevalence of hearing loss and hearing aid use by age and demographic covariates in a large, nationally representative sample of adults aged 71 years and older. Design, Setting, and Participants In this cohort study, prevalence estimates of hearing loss by age, gender, race and ethnicity, education, and income were computed using data from the 2021 National Health Aging and Trends Study. Survey weights were applied to produce nationally representative estimates to the US older population. Data were collected from June to November 2021 and were analyzed from November to December 2022. Main Outcomes and Measures Criterion-standard audiometric measures of hearing loss and self-reported hearing aid use. Results In this nationally representative sample of 2803 participants (weighted estimate, 33.1 million individuals) aged 71 years or older, 38.3% (95% CI, 35.5%-41.1%) were aged 71 to 74 years, 36.0% (95% CI, 33.1%-38.8%) were aged 75 to 79 years, 13.8% (95% CI, 12.6%-14.9%) were aged 80 to 84 years, 7.9% (95% CI, 7.2%-8.6%) were aged 85 to 89 years, and 4.0% (95% CI, 3.5%-4.6%) were aged 90 years or older; 53.5% (95% CI, 50.9%-56.1%) were female and 46.5% (95% CI, 43.9%-49.1%) were male; and 7.5% (95% CI, 6.2%-8.7%) were Black, 6.5% (95% CI, 4.4%-8.7%) were Hispanic, and 82.7% (95% CI, 79.7%-85.6%) were White. An estimated 65.3% of adults 71 years and older (weighted estimate, 21.5 million individuals) had at least some degree of hearing loss (mild, 37.0% [95% CI, 34.7%-39.4%]; moderate, 24.1% [95% CI, 21.9%-26.4%]; and severe, 4.2% [95% CI, 3.3%-5.3%]). The prevalence was higher among White, male, lower-income, and lower education attainment subpopulations and increased with age, such that 96.2% (95% CI, 93.9%-98.6%) of adults aged 90 years and older had hearing loss. Among those with hearing loss, only 29.2% (weighted estimate, 6.4 million individuals) used hearing aids, with lower estimates among Black and Hispanic individuals and low-income individuals. Conclusions and Relevance These findings suggest that bilateral hearing loss is nearly ubiquitous among older US individuals, prevalence and severity increase with age, and hearing aid use is low. Deeper consideration of discrete severity measures of hearing loss in this population, rather than binary hearing loss terminology, is warranted.
The Critical Interplay of CAF Plasticity and Resistance in Prostate Cancer
Authors: Xiaoling Li, Ping Mu
Journal: Cancer Research (2023)

Abstract Prostate cancer is a common malignancy driven by the androgen receptor (AR) pathway, with androgen deprivation therapy (ADT) being a standard treatment. However, the development of castration-resistant prostate cancer (CRPC) poses a significant challenge. CRPC is characterized by significantly increased tumor heterogeneity and lineage plasticity. Current research has primarily emphasized intrinsic tumor mechanisms, paying less attention to the role of the tumor microenvironment in cancer recurrence and drug resistance. In their recent study published in Cancer Cell, Wang and colleagues used single-cell RNA sequencing in genetically engineered mouse models with prostate tumors at different stages. They revealed that SPP1+ myofibroblastic cancer-associated fibroblasts (myCAF), induced by ADT, play an instrumental role in CRPC development. Their work also underscores the association between therapy-induced phenotypic alterations of CAFs and disease progression. This discovery highlights the potential for stromal compartment targeting as a means to mitigate CRPC development and overcome treatment resistance.
Exposure of iPSC-derived human microglia to brain substrates enables the generation and manipulation of diverse transcriptional states in vitro
Authors: Michael-John Dolan, Martine Therrien, Saša Jereb, Tushar Kamath, Vahid Gazestani, Trevor Atkeson, Samuel E. Marsh, Aleksandrina Goeva, Neal M. Lojek, Sarah Murphy, Cassandra M. White, Julia Joung, Bingxu Liu, Francesco Limone, Kevin Eggan, Nir Hacohen, Bradley E. Bernstein, Christopher K. Glass, Ville Leinonen, Mathew Blurton-Jones, Feng Zhang, Charles B. Epstein, Evan Z. Macosko, Beth Stevens
Journal: Nature Immunology (2023)

Abstract Microglia, the macrophages of the brain parenchyma, are key players in neurodegenerative diseases such as Alzheimer’s disease. These cells adopt distinct transcriptional subtypes known as states. Understanding state function, especially in human microglia, has been elusive owing to a lack of tools to model and manipulate these cells. Here, we developed a platform for modeling human microglia transcriptional states in vitro. We found that exposure of human stem-cell-differentiated microglia to synaptosomes, myelin debris, apoptotic neurons or synthetic amyloid-beta fibrils generated transcriptional diversity that mapped to gene signatures identified in human brain microglia, including disease-associated microglia, a state enriched in neurodegenerative diseases. Using a new lentiviral approach, we demonstrated that the transcription factor MITF drives a disease-associated transcriptional signature and a highly phagocytic state. Together, these tools enable the manipulation and functional interrogation of human microglial states in both homeostatic and disease-relevant contexts.
C-176 loaded Ce DNase nanoparticles synergistically inhibit the cGAS-STING pathway for ischemic stroke treatment
Authors: Zhixin Zhu, Haipeng Lu, Lulu Jin, Yong Gao, Zhefeng Qian, Pan Lu, Weijun Tong, Pik Kwan Lo, Zhengwei Mao, Haifei Shi
Journal: Bioactive Materials (2023)

The neuroinflammatory responses following ischemic stroke cause irreversible nerve cell death. Cell free-double strand DNA (dsDNA) segments from ischemic tissue debris are engulfed by microglia and sensed by their cyclic GMP-AMP synthase (cGAS), which triggers robust activation of the innate immune stimulator of interferon genes (STING) pathway and initiate the chronic inflammatory cascade. The decomposition of immunogenic dsDNA and inhibition of the innate immune STING are synergistic immunologic targets for ameliorating neuroinflammation. To combine the anti-inflammatory strategies of STING inhibition and dsDNA elimination, we constructed a DNase-mimetic artificial enzyme loaded with C-176. Nanoparticles are self-assembled by amphiphilic copolymers (P[CL35-b-(OEGMA20.7-co-NTAMA14.3)]), C-176, and Ce4+ which is coordinated with nitrilotriacetic acid (NTA) group to form corresponding catalytic structures. Our work developed a new nano-drug that balances the cGAS-STING axis to enhance the therapeutic impact of stroke by combining the DNase-memetic Ce4+ enzyme and STING inhibitor synergistically. In conclusion, it is a novel approach to modulating central nervus system (CNS) inflammatory signaling pathways and improving stroke prognosis.
Mannose‐Decorated Co‐Polymer Facilitates Controlled Release of Butyrate to Accelerate Chronic Wound Healing
Authors: Abigail L. Lauterbach, Anna J. Slezak, Ruyi Wang, Shijie Cao, Michal M. Raczy, Elyse A. Watkins, Carlos J. Medina Jimenez, Jeffrey A. Hubbell
Journal: Advanced Healthcare Materials (2023)

Abstract Butyrate is a key bacterial metabolite that plays an important and complex role in modulation of immunity and maintenance of epithelial barriers. Its translation to clinic is limited by poor bioavailability, pungent smell, and the need for high doses, and effective delivery strategies have yet to realize clinical potential. Here, a novel polymeric delivery platform for tunable and sustainable release of butyrate consisting of a methacrylamide backbone with butyryl ester or phenyl ester side chains as well as mannosyl side chains, which is also applicable to other therapeutically relevant metabolites is reported. This platform's utility in the treatment of non‐healing diabetic wounds is explored. This butyrate‐containing material modulated immune cell activation in vitro and induced striking changes in the milieu of soluble cytokine and chemokine signals present within the diabetic wound microenvironment in vivo. This novel therapy shows efficacy in the treatment of non‐healing wounds through the modulation of the soluble signals present within the wound, and importantly accommodates the critical temporal regulation associated with the wound healing process. Currently, the few therapies to address non‐healing wounds demonstrate limited efficacy. This novel platform is positioned to address this large unmet clinical need and improve the closure of otherwise non‐healing wounds.
Suppressing a phosphohydrolase of cytokinin nucleotide enhances grain yield in rice
Authors: Bi Wu, Jianghu Meng, Hongbo Liu, Donghai Mao, Huanran Yin, Zhanyi Zhang, Xiangchun Zhou, Bo Zhang, Ahmed Sherif, Haiyang Liu, Xianghua Li, Jinghua Xiao, Wenhao Yan, Lei Wang, Xingwang Li, Wei Chen, Weibo Xie, Ping Yin, Qifa Zhang, Yongzhong Xing
Journal: Nature Genetics (2023)